Gene expression profiling in response to the histone deacetylase inhibitor BL1521 in neuroblastoma
| Autor: | Rutger Meinsma, Stephan Kemp, Annemieke J.M. de Ruijter, André B.P. van Kuilenburg, Peter Bosma, Huib N. Caron |
|---|---|
| Přispěvatelé: | Paediatric Metabolic Diseases, Laboratory Genetic Metabolic Diseases, Cancer Center Amsterdam, Amsterdam Public Health, Paediatric Oncology, Amsterdam Gastroenterology Endocrinology Metabolism |
| Rok vydání: | 2005 |
| Předmět: |
medicine.drug_class
Biology Hydroxamic Acids Neuroblastoma Cell Line Tumor Gene expression medicine Humans neoplasms Oligonucleotide Array Sequence Analysis Gene Expression Profiling Histone deacetylase inhibitor Wnt signaling pathway Cell Differentiation Cell Biology Cell cycle Blotting Northern medicine.disease Gene Expression Regulation Neoplastic Histone Deacetylase Inhibitors Gene expression profiling Trichostatin A Cancer research Histone deacetylase medicine.drug |
| Zdroj: | Experimental cell research, 309(2), 451-467. Academic Press Inc. |
| ISSN: | 0014-4827 |
| Popis: | Neuroblastoma is a childhood tumor with a poor survival in advanced stage disease despite intensive chemotherapeutic regimes. The new historic deacetylase (HDAC) inhibitor BL1521 has shown promising results in neuroblastoma. Inhibition of HDAC resulted in a decrease in proliferation and metabolic activity, induction of apoptosis and differentiation of neuroblastoma cells. In order to elucidate the mechanism mediating the effects of BL1521 on neuroblastoma cells, we investigated the gene expression profile of an MYCN single copy (SKNAS) and an MYCN amplified (IMR32) neuroblastoma cell line after treatment with BL1521 using the Affymetrix oligonucleotide array U133A. An altered expression of 255 genes was observed in both neuroblastoma cell lines. The majority of these genes were involved in gene expression, cellular metabolism, and cell signaling. We observed changes in the expression of vital genes belonging to the cell cycle (cyclin D1 and CDK4) and apoptosis (BNIP3, BID, and BCL2) pathway in response to BL1521. The expression of 37 genes was altered by both BL1521 and Trichostatin A, which could indicate a common gene set regulated by different HDAC inhibitors. BL1521 treatment changed the expression of a number of MYCN-associated genes. Several genes in the Writ and the Delta/Notch pathways were changed in response to BL1521 treatment, suggesting that BL1521 is able to induce the differentiation of neuroblastoma cells into a more mature phenotype. (c) 2005 Elsevier Inc. All rights reserved |
| Databáze: | OpenAIRE |
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